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Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.

ABSTRACT: Genetic factors involved in the interindividual variability of antithrombin have not been identified. We studied two polymorphisms of the gene coding for antithrombin (SER-PINC1) in 298 Spanish Caucasian blood donors: rs3138521, a DNA length polymorphism located on the promoter region and rs2227589, a SNP located on intron 1 that has been described as a mild thrombotic risk factor. We detected a complete linkage disequilibrium between these polymorphisms (D'=0.999). The rs3138521 polymorphism has no functional consequences. However, the rs2227589 SNP significantly associated with plasma anti-FXa activity and antithrombin levels: carriers of the A allele had slightly but significantly lower anticoagulant activity and levels than GG subjects (97.0+/-7.3% vs. 94.6+/-8.4%; p=0.032; 99.5+/-5.8% vs. 94.8+/-5.6%; p=0.001; respectively). Our results identified a functional effect of the rs2227589 polymorphism not explained by its linkage with the promoter polymorphism that support the moderate thrombotic risk associated with the A allele.

SUBMITTER: Anton AI

PROVIDER: S-EPMC2663624 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.

Antón Ana I AI Teruel Raúl R Corral Javier J Miñano Antonia A Martínez-Martínez Irene I Ordóñez Adriana A Vicente Vicente V Sánchez-Vega Beatriz B

Haematologica 20090219 4

Genetic factors involved in the interindividual variability of antithrombin have not been identified. We studied two polymorphisms of the gene coding for antithrombin (SER-PINC1) in 298 Spanish Caucasian blood donors: rs3138521, a DNA length polymorphism located on the promoter region and rs2227589, a SNP located on intron 1 that has been described as a mild thrombotic risk factor. We detected a complete linkage disequilibrium between these polymorphisms (D'=0.999). The rs3138521 polymorphism ha ...[more]

PMID: 19229049

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Project description:Background and Aims: Genetic variants in the gene SERPINC1 have been shown to be associated with antithrombin deficiency, which subsequently contributes to the susceptibility to venous thrombosis. However, several other studies have shown conflicting results regarding the association of SERPINC1 gene polymorphisms (rs2227589) with the risk of thrombosis. Hence, in the present study, we conducted a case-control study to further evaluate the association between the variant rs2227589 with antithrombin deficiency in pulmonary embolism (PTE). A pooled systematic analysis was also conducted to evaluate the risk of rs2227589 in venous thromboembolism (VTE) among multiple populations. Methods: This case-control study involved 101 patients and 199 healthy controls. The allele frequency of SERPINC1 variant rs2227589 was analyzed by Sequenom assay. Antithrombin anticoagulant activity was detected using an automatic coagulation analyzer. In addition, a pooled systematic analysis on 10 cohorts consisting of 5,518 patients with VTE and 8,935 controls was performed. Results: In total, 27 (26.7%) PTE subjects were diagnosed as having antithrombin deficiency. Our results showed that antithrombin plasma activity was slightly lower in T allele carriers than that in C allele carriers. However, there was no significant correlation between rs2227589 genotype and antithrombin anticoagulant activity. The recessive model showed that rs2227589 was significantly associated (p = 0.026) with an increased risk {odds ratio [OR]: 2.31, 95% confidence interval [CI] (1.09-4.89)} of Chinese PTE. The pooled systematic analysis of all case-control study and meta-analysis showed that rs2227589 polymorphism was associated with an increased risk of VTE in the additive model [OR: 1.09, 95% CI (1.01-1.18), P = 0.029] and dominant model [OR: 1.10, 95% CI (1.01-1.20), P = 0.034]. Conclusions: Our study demonstrated that variant rs2227589 is associated with an increased risk of PTE in a Chinese population but no correlation with antithrombin anticoagulant activity. However, pooled systematic analysis of multiple populations showed a significant association between rs2227589 and the risk of VTE in the additive and dominant genetic model.

Dataset Information

Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.

Publications

Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.

Similar Datasets

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